C-phycocyanin from Limnothrix Species KNUA002 Alleviates Cisplatin-Induced Ototoxicity by Blocking the Mitochondrial Apoptotic Pathway in Auditory Cells

Abstract

Ototoxicity, or adverse pharmacological effects on the inner ear or auditory nerve, is a common side effect of cisplatin, a platinum-based drug widely used in anticancer chemotherapy. Although the incidence of ototoxicity is high among patients that receive cisplatin therapy, there is currently no effective treatment for it. The generation of excessive reactive oxygen species (ROS) is considered to be the major cause of cisplatin-induced ototoxicity. C-phycocyanin (C-PC), a blue phycobiliprotein found in cyanobacteria and red algae, has antioxidant and anticancer activities in different experimental models in vitro and in vivo. Thus, we tested the ability of C-PC from Limnothrix sp. KNUA002 to protect auditory cells from cisplatin-induced ototoxicity in vitro. Pretreatment with C-PC from Limnothrix sp. KNUA002 inhibited apoptosis and protected mitochondrial function by preventing ROS accumulation in cisplatin-treated House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, a mouse auditory cell line. Cisplatin increased the expression of Bax and reduced the expression of Bcl-2, which activate and inhibit, respectively, the mitochondrial apoptotic pathway in response to oxidative stress. Pretreatment with C-PC prior to cisplatin treatment caused the Bax and Bcl-2 levels to stay close to the levels in untreated control cells. Our results suggest that C-PC from Limnothrix sp. KNUA002 protects cells against cisplatin-induced cytotoxicity by inhibiting the mitochondrial apoptotic pathway.

Phycobiliproteins: Structural aspects, functional characteristics, and biotechnological perspectives

“…Maintains Bax and Bcl-2 levels close to untreated control. PC protection of cells against cisplatin-induced cytotoxicity as an anti-cancer therapy countermeasure [120] Spirulina sp. / Ameliorates the radiation-induced intestinal injury and regulates the effect on gut microbiota by TLR4/Myd88/NF-κB pathway Countermeasure for the radiation-induced gastrointestinal syndrome [121] Spirulina platensis / Chlorophyllin-PC mixture plus diode laser irradiation reduced the ex-vivo cariogenic biofilm of Streptococcus mutans by increasing its ROS generation.…”

Preliminary Study on the Activity of Phycobiliproteins against Botrytis cinerea

“…Phycobiliproteins (PBPs) are natural water-soluble proteins present in cyanobacteria and in the chloroplasts of some algae, such as rhodophytes, glaucophytes, and cryptomonas [1][2][3]. They are the main component of light-harvesting complex and can be classified into four types according to their spectral properties: allophycocyanins, phycocyanins, phycoerythrins, and phycoerythrocyanins [4,5].…”

Novel Application of Eupatilin for Effectively Attenuating Cisplatin-Induced Auditory Hair Cell Death via Mitochondrial Apoptosis Pathway

“…It has been demonstrated that mitochondria play a major role in ototoxic drug-induced ototoxicity, which is caused by excessive generation of ROS in hair cells [ 36 , 37 ]. We analyzed the crosstalk between eupatilin, ROS, and mitochondria using a cellular CellROX green assay and the mitochondria-specific ROS indicator MitoSOX Red.…”

“…These results confirmed the beneficial effect of eupatilin on HEI-OC1 apoptosis, suggesting that eupatilin stabilizes mitochondria and relieves the activation of mitochondriamediated apoptosis, thereby protecting cells from cisplatin-induced apoptosis. Oxidative Medicine and Cellular Longevity It has been demonstrated that mitochondria play a major role in ototoxic drug-induced ototoxicity, which is caused by excessive generation of ROS in hair cells [36,37]. We analyzed crosstalk between eupatilin, ROS, and mitochondria using a cellular CellROX green assay and the mitochondria-specific ROS indicator MitoSOX Red.…”